ADGRG6 (adhesion G protein-coupled receptor G6)

Gene

• Entrez ID: 57211
• Gene name: Adhesion G protein-coupled receptor G6
• Gene symbol: ADGRG6
• Synonyms (NCBI Gene): APG1, DREG, GPR126, LCCS9, PR126, PS1TP2, VIGR
• Chromosome: 6
• Chromosome location: 6q24.2
• Summary: This gene, which is upregulated in human umbilical vein endothelial cells, encodes a G protein-coupled receptor. Variations in this gene can affect a person`s stature. Multiple transcript variants encoding different proteins have been found for this gene.

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs749355583	C>G,T	Conflicting-interpretations-of-pathogenicity, pathogenic	Stop gained, coding sequence variant, missense variant
rs793888524	->G	Pathogenic	Frameshift variant, coding sequence variant
rs793888525	T>A,G	Pathogenic	Missense variant, coding sequence variant
rs1349317802	->T	Pathogenic	Frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT740247	hsa-miR-4762-5p	HITS-CLIP	19536157
MIRT740248	hsa-miR-7158-5p	HITS-CLIP	19536157
MIRT740249	hsa-miR-520d-5p	HITS-CLIP	19536157
MIRT740250	hsa-miR-524-5p	HITS-CLIP	19536157
MIRT740251	hsa-miR-3671	HITS-CLIP	19536157
MIRT740252	hsa-miR-607	HITS-CLIP	19536157

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001890	Process	Placenta development	ISS
GO:0004175	Function	Endopeptidase activity	TAS
GO:0004888	Function	Transmembrane signaling receptor activity	IEA
GO:0004930	Function	G protein-coupled receptor activity	IBA
GO:0004930	Function	G protein-coupled receptor activity	IDA	35394864
GO:0004930	Function	G protein-coupled receptor activity	IEA
GO:0004930	Function	G protein-coupled receptor activity	IMP	24227709
GO:0004930	Function	G protein-coupled receptor activity	ISS
GO:0004930	Function	G protein-coupled receptor activity	TAS	15203201
GO:0005518	Function	Collagen binding	ISS
GO:0005737	Component	Cytoplasm	IDA	15189448
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA	31924782
GO:0005886	Component	Plasma membrane	IDA	15189448, 24227709
GO:0005886	Component	Plasma membrane	IEA
GO:0007165	Process	Signal transduction	IEA
GO:0007166	Process	Cell surface receptor signaling pathway	IEA
GO:0007166	Process	Cell surface receptor signaling pathway	ISS
GO:0007186	Process	G protein-coupled receptor signaling pathway	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS	15203201
GO:0007188	Process	Adenylate cyclase-modulating G protein-coupled receptor signaling pathway	ISS
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	ISS
GO:0007193	Process	Adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	IDA	34239069
GO:0007193	Process	Adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	IDA	35394864
GO:0007193	Process	Adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	ISS
GO:0007399	Process	Nervous system development	TAS
GO:0009986	Component	Cell surface	IDA	15225624
GO:0014037	Process	Schwann cell differentiation	IEA
GO:0014037	Process	Schwann cell differentiation	IMP	24227709
GO:0016020	Component	Membrane	IEA
GO:0016020	Component	Membrane	TAS	15203201
GO:0022011	Process	Myelination in peripheral nervous system	IBA
GO:0022011	Process	Myelination in peripheral nervous system	ISS
GO:0030500	Process	Regulation of bone mineralization	ISS
GO:0042552	Process	Myelination	IEA
GO:0042552	Process	Myelination	IMP	26004201
GO:0043236	Function	Laminin binding	IBA
GO:0043236	Function	Laminin binding	ISS
GO:0046872	Function	Metal ion binding	IEA
GO:0050840	Function	Extracellular matrix binding	ISS
GO:0051216	Process	Cartilage development	ISS
GO:0060347	Process	Heart trabecula formation	IBA
GO:0060856	Process	Establishment of blood-brain barrier	ISS
GO:1903670	Process	Regulation of sprouting angiogenesis	ISS

Other IDs

• MIM: 612243
• HGNC: 13841
• e!Ensembl: ENSG00000112414

Protein

• UniProt ID: Q86SQ4
• Protein name: Adhesion G-protein coupled receptor G6 (Developmentally regulated G-protein-coupled receptor) (G-protein coupled receptor 126) (Vascular inducible G protein-coupled receptor) [Cleaved into: Adhesion G-protein coupled receptor G6, N-terminal fragment (ADGR
• Protein function: Adhesion G-protein coupled receptor (aGPCR) for steroid hormones, such as progesterone and 17alpha-hydroxyprogesterone (17OHP) (PubMed:35394864, PubMed:39884271). Involved in many biological processes, such as myelination, sprouting angiogenesis
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00431	CUB	41 → 146	CUB domain	Domain
  PF00354	Pentaxin	157 → 348	Pentaxin family	Domain
  PF01825	GPS	801 → 846	GPCR proteolysis site, GPS, motif	Motif
  PF00002	7tm_2	861 → 1110	7 transmembrane receptor (Secretin family)	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed in placenta and to a lower extent in pancreas and liver. Detected in aortic endothelial cells but not in skin microvascular endothelial cells. {ECO:0000269|PubMed:15225624}.
• Sequence:

  MMFRSDRMWSCHWKWKPSPLLFLFALYIMCVPHSVWGCANCRVVLSNPSGTFTSPCYPND
  YPNSQACMWTLRAPTGYIIQITFNDFDIEEAPNCIYDSLSLDNGESQTKFCGATAKGLSF
  NSSANEMHVSFSSDFSIQKKGFNASYIRVAVSLRNQKVILPQTSDAYQVSVAKSISIPEL
  SAFTLCFEATKVGHEDSDWTAFSYSNASFTQLLSFGKAKSGYFLSISDSKCLLNNALPVK
  EKEDIFAESFEQLCLVWNNSLGSIGVNFKRNYETVPCDSTISKVIPGNGKLLLGSNQNEI
  VSLKGDIYNFRLWNFTMNAKILSNLSCNVKGNVVDWQNDFWNIPNLALKAESNLSCGSYL
  IPLPAAELASCADLGTLCQATVNSPSTTPPTVTTNMPVTNRIDKQRNDGIIYRISVVIQN
  ILRHPEVKVQSKVAEWLNSTFQNWNYTVYVVNISFHLSAGEDKIKVKRSLEDEPRLVLWA
  LLVYNATNNTNLEGKIIQQKLLKNNESLDEGLRLHTVNVRQLGHCLAMEEPKGYYWPSIQ
  PSEYVLPCPDKPGFSASRICFYNATNPLVTYWGPVDISNCLKEANEVANQILNLTADGQN
  LTSANITNIVEQVKRIVNKEENIDITLGSTLMNIFSNILSSSDSDLLESSSEALKTIDEL
  AFKIDLNSTSHVNITTRNLALSVSSLLPGTNAISNFSIGLPSNNESYFQMDFESGQVDPL
  ASVILPPNLLENLSPEDSVLVRRAQFTFFNKTGLFQDVGPQRKTLVSYVMACSIGNITIQ
  NLKDPVQIKIKHTRTQEVHHPICAFWDLNKNKSFGGWNTSGCVAHRDSDASETVCLCNHF
  THFGVLMDLPRSASQLDARNTKVLTFISYIGCGISAIFSAATLLTYVAFEKLRRDYPSKI
  LMNLSTALLFLNLLFLLDGWITSFNVDGLCIAVAVLLHFFLLATFTWMGLEAIHMYIALV
  KVFNTYIRRYILKFCIIGWGLPALVVSVVLASRNNNEVYGKESYGKEKGDEFCWIQDPVI
  FYVTCAGYFGVMFFLNIAMFIVVMVQICGRNGKRSNRTLREEVLRNLRSVVSLTFLLGMT
  WGFAFFAWGPLNIPFMYLFSIFNSLQGLFIFIFHCAMKENVQKQWRQHLCCGRFRLADNS
  DWSKTATNIIKKSSDNLGKSLSSSSIGSNSTYLTSKSKSSSTTYFKRNSHTDNVSYEHSF
  NKSGSLRQCFHGQVLVKTGPC

• Sequence length: 1221

Pathways

Reactome:

EGR2 and SOX10-mediated initiation of Schwann cell myelination

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Arthrogryposis multiplex congenita	Pathogenic; Likely pathogenic	rs749355583, rs793888524, rs793888525	RCV000172977 RCV000172978 RCV000172979	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Lethal congenital contracture syndrome 9	Pathogenic; Likely pathogenic	rs2115031969, rs749355583, rs793888524, rs793888525, rs2483177661, rs926862737	RCV001839465 RCV000186598 RCV000186599 RCV000186600 RCV003988948 RCV004527244	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ADGRG6-related disorder	Benign; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CENTRAL NERVOUS SYSTEM CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL DEFORMITY OF CLAVICLE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL DEFORMITY OF ELBOW	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL DEFORMITY OF FOREARM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL DEFORMITY OF SCAPULA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL DEFORMITY OF WRIST	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL DISLOCATION OF ELBOW	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL DISLOCATION OF GLENOHUMERAL JOINT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIFFERENTIATED THYROID CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ENDOMETRIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INFLAMMATORY BOWEL DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTELLECTUAL DISABILITY	—	Disgenet, GenCC Disgenet, GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LETHAL CONGENITAL CONTRACTURE SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung adenocarcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERIPHERAL ARTERIAL DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS, ISOLATED, SUSCEPTIBILITY TO, 1	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma of lung (disorder)	Lung adenocarcinoma	BEFREE	31382924		★☆☆☆☆ Found in Text Mining only
Aggressive Periodontitis	Aggressive Periodontitis	BEFREE	27509131		★☆☆☆☆ Found in Text Mining only
Androgen-Insensitivity Syndrome	Androgen-Insensitivity Syndrome	BEFREE	25479386, 25954032, 28198779, 30886859, 31079250		★☆☆☆☆ Found in Text Mining only
Arthrogryposis	Arthrogryposis multiplex congenita	BEFREE	26004201		★☆☆☆☆ Found in Text Mining only
Arthrogryposis	Arthrogryposis	Pubtator	26004201, 33820833	Associate	★☆☆☆☆ Found in Text Mining only
Arthrogryposis	Arthrogryposis multiplex congenita	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Bladder Neoplasm	Bladder Neoplasm	BEFREE	30755618		★☆☆☆☆ Found in Text Mining only
Bone Diseases Developmental	Bone disease	Pubtator	33820833	Associate	★☆☆☆☆ Found in Text Mining only
Calcinosis	Calcinosis	Pubtator	27509131	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	30755618		★☆☆☆☆ Found in Text Mining only
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	GWASCAT_DG	28166215, 30804561, 30940143		★☆☆☆☆ Found in Text Mining only
Congenital clubfoot	Congenital Clubfoot	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital contracture	Congenital contracture	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of lung	Pulmonary hypoplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital pectus excavatum	Congenital Pectus Excavatum	BEFREE	25954032		★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	37270806	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	30549416, 31215653		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intervertebral Disc Degeneration	Intervertebral Disc Degeneration	BEFREE	31652254		★☆☆☆☆ Found in Text Mining only
LETHAL CONGENITAL CONTRACTURE SYNDROME 9	Lethal Congenital Contracture Syndrome	GENOMICS_ENGLAND_DG	26004201		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
LETHAL CONGENITAL CONTRACTURE SYNDROME 9	Lethal Congenital Contracture Syndrome	UNIPROT_DG	26004201		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
LETHAL CONGENITAL CONTRACTURE SYNDROME 9	Lethal Congenital Contracture Syndrome	BEFREE	30549416		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
LETHAL CONGENITAL CONTRACTURE SYNDROME 9	Lethal Congenital Contracture Syndrome	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
LETHAL CONGENITAL CONTRACTURE SYNDROME 9	Lethal Congenital Contracture Syndrome	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	27258612	Associate	★☆☆☆☆ Found in Text Mining only
Lung Diseases	Lung disease	Pubtator	20010835, 26635082	Associate	★☆☆☆☆ Found in Text Mining only
Lung diseases	Lung Diseases	BEFREE	26635082, 31215653		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	37154297	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	BEFREE	30755618		★☆☆☆☆ Found in Text Mining only
Marfan Syndrome	Marfan syndrome	Pubtator	37270806	Associate	★☆☆☆☆ Found in Text Mining only
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	BEFREE	30904492		★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	30755618, 31382924		★☆☆☆☆ Found in Text Mining only
Neuromuscular Diseases	Neuromuscular Diseases	BEFREE	26578207		★☆☆☆☆ Found in Text Mining only
Neuromuscular Diseases	Neuromuscular disease	Pubtator	26578207	Associate	★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	31382924		★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	26917578, 37734371, 39650745	Associate	★☆☆☆☆ Found in Text Mining only
Scoliosis	Scoliosis	Pubtator	37270806	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Scoliosis, unspecified	Scoliosis	GWASDB_DG	23666238		★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	GWASCAT_DG	23666238		★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	31391008	Associate	★☆☆☆☆ Found in Text Mining only
Testicular Germ Cell Tumor	Testicular Germ Cell Tumor	BEFREE	11389747		★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	30401719, 30755618, 36658180, 37081791	Associate	★☆☆☆☆ Found in Text Mining only